Monday 23rd April 2012

A sea change of attitude among leading researchers about the importance of FIV infection among lions? Yes it was, and will now perhaps lead to a better investigation of the effects of this pernicious disease that could significantly influence conservation priorities of remaining lion populations.

In a recent article Emerging Viruses in the Felidae: Shifting Paradigms in the journal Viruses (7 Feb 2012, v4, pp 236-257) Steve O’Brien and his colleagues indicated a rather big shift in their previous paradigm about the effect of FIV on lions. For many years, O’Brien had been a foremost proponent of FIV infection being inconsequential among lions – after all, his research group had shown that the virus had most likely infected lions for many thousands of years, and despite high infection rates in places like the Serengeti and the Okavango, lions did not seem to be displaying negative effects. This view ignored some important pathological data gathered from an Italian zoo lion infected with FIV (Poli et al, 1995, J. Wildl. Diseases 31(1): 70-74) and immune system information from lions provided by Kennedy-Stoskopf since 1994. Basically, those studies contested what O’Brien and colleagues had been saying and were repeating, and indicated similar pathologies and consequences of infection to those among domestic cats that should have been taken seriously.

Niels Pedersen, a friend at the University of California School of Veterinary Medicine, was the first to discover the Feline Immunodeficiency Virus in 1986. He was able to isolate this “new” virus from a domestic cat brought in to the Veterinary Hospital presenting symptoms and signs he recognized from monkeys infected with Simian Immunodeficiency Virus. Once the cat immunodeficiency virus was described, it became clear that the infection showed a similar progression of immune system compromise as had been noted among humans affected with HIV. Consequently, with an animal model, a great number of experimental protocols could and were designed with domestic cats to determine outcomes of infection with an immunodeficiency virus. Niels never believed that infection with such a virus could be inconsequential among lions.

Meanwhile, O’Brien and his co-workers (including virologists and veterinarians) seemed unaware of the very many journal articles detailing a great diversity of consequences of infection with FIV among domestic cats. Instead of using such information as a possible model of infection consequence among lions, they felt that lions had worked out some sort of “truce” with the virus. Why did they take this track?

First, O’Brien and his colleagues looked at the divergent genetic sequences of the FIV strains infecting lions, and came to the conclusion that this was an old association between this virus and a big cat (perhaps over 300,000 years?). Making another leap, they decided that all long-term associations between a virus and host inevitably resulted in a compromise – and used examples like measles and smallpox for example. There are of course elements of truth in this, as selection works on host immune systems to become better resistant to viruses and also on viruses to diminish the lethal effects on their hosts so the viruses have the opportunity to spread. But that is not the way immunodeficiency viruses operate – they mutate rapidly, shuffle parts of genomes among co-infecting FIV strains, and are not in themselves immediately lethal. Selection on an immunodeficiency virus has more to do with better avoidance of immune responses than accommodating longevity of the host. That is already built into the virus modus operandi (see below).

Second, O’Brien et al were looking for an immunodeficiency virus/host association that was not greatly negative to the host to perhaps decipher genetic mechanisms for resistance. This would then lead to a better understanding of how HIV infection among human populations could perhaps be mitigated. Direct studies of human populations had already led to an understanding that western Europeans had higher levels of resistance to HIV infection than, say, African populations. O’Brien and colleagues attributed this to possible effects of exposure by Europeans to a great diversity of pathogens in the past – for example the numerous outbreaks of plague in the Middle Ages that perhaps fortuitously selected for a particular genetic makeup among survivors - that then provided a better chance of surviving the future challenge of HIV centuries later. But any hopeful level of accommodation with FIV was not to be found among lions.

Third, researchers wrongly interpreted the way immunodeficiency viruses actually affect their hosts. Proof of infection via antibody analyses proved to be at very high levels in some populations – close to all adult lions in the Okavango and the Serengeti for example. But lions were not dying in huge numbers, and infected individuals seemed perfectly healthy for years after they had been diagnosed positive. Surprise, surprise? Not really, as that is the way the virus works. After an initial illness following infection, the virus then settles down to work slowly (it is after all a lentivirus) but inexorably to erode the immune system. Animals and humans can indeed seem apparently healthy for years after first infection as the immune system remains largely functional and is perhaps supplemented by a variety of secondary defence mechanisms (e.g. hormones, B-cell activation mechanisms independent of T-cells). FIV infection among lion populations thus did not present as an epidemic. This should have been expected, but instead it was used as evidence for co-adaptation and justification for misplaced hypotheses.

In hindsight, it was compromised science. After negating the consequences of FIV infection among lions for many years, and therefore significantly supporting the hopeful view that the infection was inconsequential, O’Brien and his colleagues finally acknowledged some cracks in the façade. In the paper mentioned above, O’Brien admitted that their past conclusions were premature and oversimplified. He refers to a study undertaken by Melody Roelke (a veterinarian in his group) among Botswana lions and added the following remarks:

b) In addition, there were multiple elevations of opportunistic infections… further, spleen and lymph node biopsies from nine free-ranging lions revealed evidence of lymphoid depletion, a hallmark of AIDS in human[s], cats, and macaques [a primate] … these findings strongly suggest FIV is contributing to the loss of immune competence among these lions;

c) These observations would suggest that infection with FIV … might have increased the risk of mortality upon secondary CDV [Canine Distemper Virus] infection [during the CDV outbreak in the 1990s];

d) … the striking influence of FIV on lion immune function … clinical disposition, and a potential ancillary role in CDV mortality … affirms that FIV is likely pathogenic among lions … FIV is a potentially harmful agent in free-ranging lions, as for housecats, and deserves further scrutiny in the other free-ranging species afflicted with FIV.”

While this is good news for a belated recognition of the importance of FIV infections among lions and their resulting fragility, it also places FIV back in the mainstream of concerns for the future survival of lions. There are perhaps five or six populations of lions that number over 1000 individuals of all ages. On these populations rests the hope for the future survival of the species in Africa, and they largely occur in protected areas. Such populations are not protected from disease, and cannot be cured of FIV. Future conservation and management of the species can now move on to incorporate disease components with the brave admission from O’Brien’s research group that what they said in the past about the consequences of FIV infection among lions was “premature and oversimplified”.

We now need to move forward in a united determination to design the best conservation plans for this greatly threatened species. The threat from disease can finally unanimously be taken seriously among FIV compromised populations (basically all the five or six large populations mentioned above), and must be included in all conservation programmes as now there can be no more distractors.